You may be trying to access this site from a secured browser on the server. Please enable scripts and reload this page.

Enter your Email address:

Wolters Kluwer Health may email you for journal alerts and information, but is committed
to maintaining your privacy and will not share your personal information without
your express consent. For more information, please refer to our Privacy Policy.

Abstract

Objective: Hypertension is associated with an increased cancer mortality and a higher kidney cancer risk. Blood pressure regulating hormones, such as the peptide hormone angiotensin II (AngII), are elevated in hypertension. AngII showed DNA-damaging effects in vitro and in the ex-vivo perfused mouse kidney. Here, the effect of rising doses of AngII was analysed for their genotoxic effects in vivo.

Methods: In C57BL/6-mice equipped with osmotic mini pumps, delivering AngII in four different concentrations between 60 ng/kg per min and 1 μg/kg per min during 28 days, the oxidative and DNA damaging effects of AngII were studied, using immunohistochemistry and mass spectrometry.

Results: AngII increased the SBP for up to 38 mmHg over control and adversely affected the kidney function of the mice. In the heart, at the highest dose administered, a significant increase of reactive oxygen species formation (1.4-fold over control) and double-strand breaks could be detected (13-fold over control). In the kidney, a dose-dependent increase of superoxide formation (up to 1.7-fold over control), double-strand breaks (up to 4.7-fold over control) and the mutagenic DNA base modification 7,8-dihydro-8-oxo-guanine (8-oxodG, up to 3.6-fold over control) was observed. Adverse effects already appeared at lower AngII doses, which did not raise the blood pressure. Administration of the radical scavenger tempol significantly decreased oxidative stress (by 20%) in the kidney and DNA double-strand breaks in the kidney by 60% and in the heart by 52%, without being able to lower the blood pressure.

Conclusion: This study for the first time shows oxidative stress mediated genotoxic effects of AngII in vivo. Furthermore, the increase of 8-oxodG suggests a mutagenic potential of an activated renin–angiotensin–aldosterone system, which is often found in hypertensive patients.

Enter and submit the email address you registered with. An email with instructions to reset your password will be sent to that address.

Email:

Password Sent

Link to reset your password has been sent to specified email address.

Remember me

What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
computer.

To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.

What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.